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Targeting CD301⁺ macrophages inhibits endometrial fibrosis and improves pregnancy outcome.

ABSTRACT: Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301⁺ macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single-cell RNA sequencing, bulk RNA sequencing, and experimental verification. Increasing CD301⁺ macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts and resulted in extracellular matrix accumulation, which destroyed the physiological architecture of endometrial tissue, drove endometrial fibrosis, and ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, CD301⁺ macrophages secreted GAS6 to activate the AXL/NF-κB pathway, upregulating the profibrotic protein synthesis. Targeted deletion of CD301⁺ macrophages or inhibition of AXL by Bemcentinib blunted the pathology and improved the outcomes of pregnancy in mice, supporting the therapeutic potential of targeting CD301⁺ macrophages for treating endometrial fibrosis.

SUBMITTER: Lv H

PROVIDER: S-EPMC10493587 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Targeting CD301<sup>+</sup> macrophages inhibits endometrial fibrosis and improves pregnancy outcome.

Lv Haining H Sun Haixiang H Wang Limin L Yao Simin S Liu Dan D Zhang Xiwen X Pei Zhongrui Z Zhou Jianjun J Wang Huiyan H Dai Jianwu J Yan Guijun G Ding Lijun L Wang Zhiyin Z Cao Chenrui C Zhao Guangfeng G Hu Yali Y

EMBO molecular medicine 20230731 9

Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301<sup>+</sup> macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single-cell RNA sequencing, bul ...[more]

PMID: 37519221

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Project description:PurposeAdenomyosis has a negative impact on female fertility. GnRH agonist treatment can improve pregnancy outcomes in women with adenomyosis. However, the impact of GnRH agonist upon endometrium receptivity of patients with adenomyosis remains unclear. In this study, endometrial receptivity and pregnancy outcome were investigated using a mouse model of adenomyosis.Materials and methodsAdenomyosis was induced in 12 female ICR mice, neonatally treated with tamoxifen, while another six female mice (control group) received solvent only. At 75 days, the induced adenomyosis group was randomly divided into two groups: an untreated group and a group treated with GnRH agonist (n = 6 each). Sixty days later, the mice were mated and pregnancy outcomes were observed and compared among the three groups (n = 6 each). In a parallel experiment using the same treatment regimes, uterus samples were collected on day 4 of pregnancy for immunohistochemistry, gene (quantitative polymerase chain reaction) and protein expression (Western blot), and scanning electron microscopy analyses.ResultsWe found that the average live litter size was reduced in the adenomyosis compared with control group (8 ± 0.56 versus 13 ± 0.71; P = 0.03). However, the litter size was significantly increased in the treated with GnRH agonist group compared with the untreated group (12 ± 0.35 versus 8 ± 0.56; P = 0.04). The uterine expression levels of Hoxa10, Hoxa11, Lif and integrin b3 mRNA and protein were decreased in the adenomyosis group, and were significantly increased after GnRH agonist treatment. Additionally, pinopodes were reduced in number and poorly developed in mice with induced adenomyosis. However, pinopodes were abundant and well-developed in the GnRH agonist treatment group.ConclusionAdenomyosis may have an adverse impact on endometrial receptivity and reduce pregnancy outcomes in mice. However, GnRH agonist may improve the pregnancy outcome by partially restoring endometrial receptivity.

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Targeting CD301⁺ macrophages inhibits endometrial fibrosis and improves pregnancy outcome.

Publications

Targeting CD301<sup>+</sup> macrophages inhibits endometrial fibrosis and improves pregnancy outcome.

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Dataset Information

Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome.

Publications

Targeting CD301<sup>+</sup> macrophages inhibits endometrial fibrosis and improves pregnancy outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Targeting CD301⁺ macrophages inhibits endometrial fibrosis and improves pregnancy outcome.